5470 lines
463 KiB
Text
5470 lines
463 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *516020 - CYTOCHROME b OF COMPLEX III; MTCYB
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=516020"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*516020</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/516020">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000198727;t=-" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://mitomap.org/bin/view.pl/Main/SearchSite?search=MT-CYB" class="mim-tip-hint" title="A curated repository of published and unpublished data on human mitochondrial DNA variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MITOMAP', 'domain': 'mitomap.org'})">MITOMAP</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4519" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=516020" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000198727;t=-" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=516020" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/MT-CYB" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/194303445,251831119,408360043" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/P00156" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=4519" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000198727;t=-" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=MT-CYB" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=MT-CYB" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+4519" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/MT-CYB" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:4519" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/4519" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7427" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/mt-cyb" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=516020[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=516020[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/MT-CYB/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000198727" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=MT-CYB" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=MT-CYB" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MT-CYB&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA31234" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:7427" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0013678.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:102501" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/MT-CYB#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:102501" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/4519/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002407/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=4519" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4519" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=MT-CYB&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 267044007, 447292006, 58610003<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> H47.22<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
516020
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CYTOCHROME b OF COMPLEX III; MTCYB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
COMPLEX III, CYTOCHROME b SUBUNIT<br />
|
|
UBIQUINONE-CYTOCHROME c OXIDOREDUCTASE, CYTOCHROME b SUBUNIT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MT-CYB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MT-CYB</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Cytochrome b (MTCYB) is the only mitochondrial DNA (mtDNA) encoded subunit of respiratory Complex III (ubiquinol:ferrocytochrome c oxidoreductase, or cytochrome bc1, complex, <a href="https://enzyme.expasy.org/EC/1.10.2.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.10.2.2</a>). Complex III is located within the mitochondrial inner membrane and is the second enzyme in the electron transport chain of mitochondrial oxidative phosphorylation. It catalyzes the transfer of electrons from ubiquinol (reduced Coenzyme Q10) to cytochrome c and utilizes the energy to translocate protons from inside the mitochondrial inner membrane to outside. Bovine Complex III has been resolved into 11 polypeptides by SDS-polyacrylamide gels (PAGE), designated I-XI (<a href="#45" class="mim-tip-reference" title="Schagger, H., Link, T. A., Engel, W. D., von Jagow, G. <strong>Isolation of the eleven protein subunits of the bc1 complex from beef heart.</strong> Methods Enzymol. 126: 224-237, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2856130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2856130</a>] [<a href="https://doi.org/10.1016/s0076-6879(86)26024-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2856130">Schagger et al., 1986</a>; <a href="#20" class="mim-tip-reference" title="Gonzalez-Halphen, D., Lindorfer, M. A., Capaldi, R. A. <strong>Subunit arrangement in beef heart complex III.</strong> Biochemistry 27: 7021-7031, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848575</a>] [<a href="https://doi.org/10.1021/bi00418a053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2848575">Gonzalez-Halphen et al., 1988</a>). These subunits include core proteins I and II, cytochrome b (subunit III), cytochrome c1 (subunit IV), the Rieske iron-sulfur protein (subunit V), and several smaller polypeptides. Subunits III, IV, and V are the major redox proteins in the complex and are present in the molar ratio 2:1:1 (<a href="#43" class="mim-tip-reference" title="Rieske, J. S. <strong>Composition, structure, and function of complex III of the respiratory chain.</strong> Biochim. Biophys. Acta 456: 195-247, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/788795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">788795</a>] [<a href="https://doi.org/10.1016/0304-4173(76)90012-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="788795">Rieske, 1976</a>). The core proteins I and II are essential for the assembly and proper association of the redox centers in Complex III, though they do not contain redox centers (<a href="#30" class="mim-tip-reference" title="Linke, P., Weiss, H. <strong>Reconstitution of ubiquinol-cytochrome c reductase from Neurospora mitochondria with regard to subunits I and II.</strong> Methods Enzymol. 126: 201-210, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2856127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2856127</a>] [<a href="https://doi.org/10.1016/s0076-6879(86)26022-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2856127">Linke and Weiss, 1986</a>; <a href="#12" class="mim-tip-reference" title="Crivellone, M. D., Wu, M., Tzagoloff, A. <strong>Assembly of the mitochondrial membrane system. Analysis of structural mutants of the yeast coenzyme QH2-cytochrome c reductase complex..</strong> J. Biol. Chem. 263: 14323-14333, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2844766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2844766</a>]" pmid="2844766">Crivellone et al., 1988</a>; <a href="#40" class="mim-tip-reference" title="Oudshoorn, P., Van Steeg, H., Swinkels, B. W., Schoppink, P., Grivell, L. A. <strong>Subunit II of yeast QH2:cytochrome-c oxidoreductase. Nucleotide sequence of the gene and features of the protein..</strong> Europ. J. Biochem. 163: 97-103, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3028797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3028797</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1987.tb10741.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3028797">Oudshoorn et al., 1987</a>; <a href="#48" class="mim-tip-reference" title="Tzagoloff, A., Wu, M. A., Crivellone, M. <strong>Assembly of the mitochondrial membrane system. Characterization of COR1, the structural gene for the 44-kilodalton core protein of yeast coenzyme QH2-cytochrome c reductase.</strong> J. Biol. Chem. 261: 17163-17169, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3023384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3023384</a>]" pmid="3023384">Tzagoloff et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2848575+2844766+3028797+2856130+2856127+3023384+788795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>MTCYB is a highly evolutionarily conserved, hydrophobic protein containing 8 or 9 transmembrane domains and 2 heme groups. The 2 hemes differ in redox potential and difference spectra and have been designated b-562--the high potential heme, and b-566--the low potential heme (<a href="#17" class="mim-tip-reference" title="Esposti, M. D., De Vries, S., Crimi, M., Ghelli, A., Patarnello, T., Meyer, A. <strong>Mitochondrial cytochrome b: evolution and structure of the protein.</strong> Biochim. Biophys. Acta 1143: 243-271, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8329437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8329437</a>] [<a href="https://doi.org/10.1016/0005-2728(93)90197-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8329437">Esposti et al., 1993</a>; <a href="#54" class="mim-tip-reference" title="Wikstrom, M., Krab, K., Saraste, M. <strong>Proton-translocating cytochrome complexes.</strong> Annu. Rev. Biochem. 50: 623-655, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6267990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6267990</a>] [<a href="https://doi.org/10.1146/annurev.bi.50.070181.003203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6267990">Wikstrom et al., 1981</a>; <a href="#44" class="mim-tip-reference" title="Saraste, M. <strong>Location of haem-binding sites in the mitochondrial cytochrome b.</strong> FEBS Lett. 166: 367-372, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6363134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6363134</a>] [<a href="https://doi.org/10.1016/0014-5793(84)80114-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6363134">Saraste, 1984</a>). Cytochrome b together with core proteins I and II comprise the central components of Complex III. The Rieske iron-sulfur protein is on the cytoplasmic side of the inner membrane and accepts electrons from MTCYB (<a href="#20" class="mim-tip-reference" title="Gonzalez-Halphen, D., Lindorfer, M. A., Capaldi, R. A. <strong>Subunit arrangement in beef heart complex III.</strong> Biochemistry 27: 7021-7031, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848575</a>] [<a href="https://doi.org/10.1021/bi00418a053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2848575">Gonzalez-Halphen et al., 1988</a>). The electrons are then transferred to cytochrome c1 which contains 1 membrane-spanning domain, a covalently bound heme, and is also located on the outside of the mitochondrial inner membrane. Cytochrome c1 transfers electrons to cytochrome c (<a href="#52" class="mim-tip-reference" title="Weiss, H., Linke, P., Haiker, H., Leonard, K. <strong>Structure and function of the mitochondrial ubiquinol: cytochrome c reductase and NADH: ubiquinone reductase.</strong> Biochem. Soc. Trans. 15: 100-102, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3030833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3030833</a>] [<a href="https://doi.org/10.1042/bst0150100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3030833">Weiss et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8329437+2848575+6363134+6267990+3030833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The mechanism by which proton translocation is linked to electron transport has been studied intensively for Complex III. Two important models are the proton-motive ubiquinone (Q) cycle and the b-cycle (<a href="#32" class="mim-tip-reference" title="Mitchell, P. <strong>Possible molecular mechanisms of the proton motive function of cytochrome systems.</strong> J. Theor. Biol. 62: 327-347, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/186667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">186667</a>] [<a href="https://doi.org/10.1016/0022-5193(76)90124-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="186667">Mitchell, 1976</a>; <a href="#21" class="mim-tip-reference" title="Hatefi, Y. <strong>The mitochondrial electron transport and oxidative phosphorylation system.</strong> Annu. Rev. Biochem. 54: 1015-1069, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2862839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2862839</a>] [<a href="https://doi.org/10.1146/annurev.bi.54.070185.005055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2862839">Hatefi, 1985</a>). Both models link proton translocation and electron transfer through ubiquinone redox intermediates (<a href="#21" class="mim-tip-reference" title="Hatefi, Y. <strong>The mitochondrial electron transport and oxidative phosphorylation system.</strong> Annu. Rev. Biochem. 54: 1015-1069, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2862839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2862839</a>] [<a href="https://doi.org/10.1146/annurev.bi.54.070185.005055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2862839">Hatefi, 1985</a>; <a href="#55" class="mim-tip-reference" title="Wikstrom, M., Krab, K. <strong>The semiquinone cycle. A hypothesis of electron transfer and proton translocation in cytochrome bc-type complexes.</strong> J. Bioenerg. Biomembr. 18: 181-193, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3015895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3015895</a>] [<a href="https://doi.org/10.1007/BF00743463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3015895">Wikstrom and Krab, 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=186667+2862839+3015895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>MTCYB is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 14747 and 15887 (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#49" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). It is maternally inherited along with the mtDNA (<a href="#19" class="mim-tip-reference" title="Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C. <strong>Maternal inheritance of human mitochondrial DNA.</strong> Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>] [<a href="https://doi.org/10.1073/pnas.77.11.6715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6256757">Giles et al., 1980</a>; <a href="#10" class="mim-tip-reference" title="Case, J. T., Wallace, D. C. <strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong> Somat. Cell Genet. 7: 103-108, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>] [<a href="https://doi.org/10.1007/BF01544751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261411">Case and Wallace, 1981</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6256757+7219534+6261411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The MTCYB gene encompasses 1140 nps of mtDNA and encodes a single polypeptide without introns. The mRNA has a 4-np, 5-prime noncoding region followed by the AUG start codon, and ends with the U of the UAA termination codon (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#36" class="mim-tip-reference" title="Ojala, D., Montoya, J., Attardi, G. <strong>tRNA punctuation model of RNA processing in human mitochondria.</strong> Nature 290: 470-474, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>] [<a href="https://doi.org/10.1038/290470a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219536">Ojala et al., 1981</a>; <a href="#34" class="mim-tip-reference" title="Montoya, J., Ojala, D., Attardi, G. <strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong> Nature 290: 465-470, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219535</a>] [<a href="https://doi.org/10.1038/290465a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219535">Montoya et al., 1981</a>; <a href="#49" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). It is transcribed as a part of the polycistronic H-strand transcript, flanked by the tRNAGlu and tRNAThr transcripts. These tRNAs are cleaved out at the transcript freeing transcript 11, the MTCYB mRNA. The mRNA is then polyadenylated completing the termination codon (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#36" class="mim-tip-reference" title="Ojala, D., Montoya, J., Attardi, G. <strong>tRNA punctuation model of RNA processing in human mitochondria.</strong> Nature 290: 470-474, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>] [<a href="https://doi.org/10.1038/290470a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219536">Ojala et al., 1981</a>: <a href="#6" class="mim-tip-reference" title="Attardi, G., Chomyn, A., Montoya, J., Ojala, D. <strong>Identification and mapping of human mitochondrial genes.</strong> Cytogenet. Cell Genet. 32: 85-98, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>] [<a href="https://doi.org/10.1159/000131689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7140372">Attardi et al., 1982</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7219534+7140372+7219535+7219536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The predicted molecular weight (MW) of MTCYB is 42.7 kD (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#49" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). However, its high hydrophobicity results in variable migration on SDS-PAGE with an altered apparent molecular weight. Using Tris-glycine buffer it migrates at approximately 27.5 kD (<a href="#38" class="mim-tip-reference" title="Oliver, N. A., McCarthy, J., Wallace, D. C. <strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong> Somat. Cell Molec. Genet. 10: 639-643, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>] [<a href="https://doi.org/10.1007/BF01535230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438810">Oliver et al., 1984</a>; <a href="#39" class="mim-tip-reference" title="Oliver, N. A., Wallace, D. C. <strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong> Molec. Cell. Biol. 2: 30-41, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>] [<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6955589">Oliver and Wallace, 1982</a>; <a href="#50" class="mim-tip-reference" title="Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J. <strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong> Am. J. Hum. Genet. 38: 461, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>]" pmid="3518425">Wallace et al., 1986</a>), whereas in urea-phosphate buffer it migrates at about 29 kD (<a href="#11" class="mim-tip-reference" title="Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G. <strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong> Nature 314: 592-597, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3921850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3921850</a>] [<a href="https://doi.org/10.1038/314592a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3921850">Chomyn et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3518425+6955589+6438810+7219534+3921850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Restriction site polymorphisms have been identified at the following nucleotide position for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, <a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>): Alu I: +14899, +15245, +15437, +15606, -15776; Ava II: +15487, +15591, +15882; Dde I: +14773, +14923, -15073, -15238, -15250, +15434, +15660, +15727, +15751/15754; Hae II: -14858, -15002; Hae III: +14749, +14899, -15047, -15073, -15172, +15431, +15520, +15595, -15883; Hha I: -14859, -15003; HincII: +14648/15765; HinfI: +15005, -15234, -15375, -15723; Mbo I: +14749, -14869, -15060, +15195/15221, +15235, +15397, -15591, +15790/16373; Msp I: +15485; Rsa I: +15346, +15412, -15812, +15872; Taq I: -14956, +15549, +15861; Xho I: -15068 (<a href="#49" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>MTCYB has phenotypically relevant alleles that contribute to Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>), including MTCYB*LHON15257A (<a href="#0001">516020.0001</a>) and MTCYB*LHON15812A (<a href="#0002">516020.0002</a>).</p><p><a href="#47" class="mim-tip-reference" title="Spiro, A. J., Moore, C. L., Prineas, J. W., Strasberg, P. M., Rapin, I. <strong>A cytochrome-related inherited disorder of the nervous system and muscle.</strong> Arch. Neurol. 23: 103-112, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5430330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5430330</a>] [<a href="https://doi.org/10.1001/archneur.1970.00480260009002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5430330">Spiro et al. (1970)</a> described a 46-year-old man and his 16-year-old son with progressive ataxia, predominantly proximal muscle weakness, areflexia, extensor plantar responses, dementia, and concomitant nonspecific myopathic and neuropathic changes in muscle. Studies of muscle mitochondria showed very loose coupling of oxidative phosphorylation and marked reduction in cytochrome b content, representing a defect in complex III. <a href="#35" class="mim-tip-reference" title="Morgan-Hughes, J. A., Hayes, D. J., Clark, J. B., Landon, D. N., Swash, M., Stark, R. J., Rudge, P. <strong>Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain.</strong> Brain 105: 553-582, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7104666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7104666</a>] [<a href="https://doi.org/10.1093/brain/105.3.553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7104666">Morgan-Hughes et al. (1982)</a> reported a patient with a defect at the cytochrome b level in the mitochondrial respiratory chain. The patient had onset of myoclonus followed by generalized weakness, ataxia, and mental confusion. Patients with complex III deficiency reported by <a href="#13" class="mim-tip-reference" title="Darley-Usmar, V. M., Kennaway, N. G., Buist, N. R. M., Capaldi, R. A. <strong>Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis.</strong> Proc. Nat. Acad. Sci. 80: 5103-5106, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6308671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6308671</a>] [<a href="https://doi.org/10.1073/pnas.80.16.5103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6308671">Darley-Usmar et al. (1983)</a> and <a href="#22" class="mim-tip-reference" title="Hayes, D. J., Lecky, B. R. F., Landon, D. N., Morgan-Hughes, J. A., Clark, J. B. <strong>A new mitochondrial myopathy: biochemical studies revealing a deficiency in the cytochrome b-c1 complex (complex III) of the respiratory chain.</strong> Brain 107: 1165-1177, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6095966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6095966</a>] [<a href="https://doi.org/10.1093/brain/107.4.1165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6095966">Hayes et al. (1984)</a> had combinations of muscular weakness, ataxia, exercise intolerance, and ocular myopathy. Most problems were initially noted in childhood and worsened with age. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6095966+5430330+7104666+6308671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S. <strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong> New Eng. J. Med. 341: 1037-1044, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502593</a>] [<a href="https://doi.org/10.1056/NEJM199909303411404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502593">Andreu et al. (1999)</a> described 5 new patients with exercise intolerance in whom they identified mutations in the MTCYB gene, and reviewed the characteristics of 4 patients previously identified. They concluded that there is a sporadic form of mitochondrial myopathy in which exercise intolerance is the predominant symptom. Each of the mutations in the MTCYB gene impaired the enzymatic function of the cytochrome b protein. In these patients, the clinical manifestations included progressive exercise intolerance, proximal limb weakness, and in some cases attacks of myoglobinuria. There was no maternal inheritance and there were no mutations in tissues other than muscle. The absence of these findings suggested that the disorder is due to somatic mutations in myogenic stem cells after germ-layer differentiation. All of the point mutations involved the substitution of adenine for guanine, but all were in different locations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G. <strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong> Am. J. Hum. Genet. 67: 1400-1410, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11047755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11047755</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11047755[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11047755">Keightley et al. (2000)</a> stated that the report by <a href="#16" class="mim-tip-reference" title="Dumoulin, R., Sagnol, I., Ferlin, T., Bozon, D., Stepien, G., Mousson, B. <strong>A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance.</strong> Molec. Cell Probes 10: 389-391, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8910895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8910895</a>] [<a href="https://doi.org/10.1006/mcpr.1996.0053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8910895">Dumoulin et al. (1996)</a> was the first instance of isolated complex III deficiency in which mutation in the cytochrome b gene was shown to be pathogenic, after which 12 additional pathogenic mutations in this gene were described in various studies. Most of the patients presented with the predominant feature of severe exercise intolerance, sometimes including muscle weakness and/or myoglobinuria. <a href="#27" class="mim-tip-reference" title="Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G. <strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong> Am. J. Hum. Genet. 67: 1400-1410, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11047755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11047755</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11047755[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11047755">Keightley et al. (2000)</a> reinvestigated a young woman, originally reported by <a href="#28" class="mim-tip-reference" title="Kennaway, N. G., Buist, N. R., Darley-Usmar, V. M., Papadimitriou, A., Dimauro, S., Kelley, R. I., Capaldi, R. A., Blank, N. K., D'Agostino, A. <strong>Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain.</strong> Pediat. Res. 18: 991-999, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093035</a>] [<a href="https://doi.org/10.1203/00006450-198410000-00017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6093035">Kennaway et al. (1984)</a>, who presented with exercise intolerance and lactic acidosis associated with severe deficiency of complex III and who responded to therapy with menadione and ascorbate. She gradually developed symptoms of a mitochondrial encephalomyopathy. Immunocytochemistry of serial sections of muscle showed a mosaic of fibers that reacted poorly with antibodies to subunits of complex III but reacted normally with antibodies to subunits of complex I, II, or IV, suggesting a mutation of mtDNA. This experience demonstrated the diagnostic value of immunocytochemistry in identifying specific respiratory-chain deficiencies and, potentially, distinguishing between nuclear- and mtDNA-encoded defects. <a href="#27" class="mim-tip-reference" title="Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G. <strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong> Am. J. Hum. Genet. 67: 1400-1410, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11047755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11047755</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11047755[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11047755">Keightley et al. (2000)</a> demonstrated a stop codon mutation, 15242G-A (<a href="#0007">516020.0007</a>), in the mtDNA-encoded cytochrome b gene, resulting in loss of the last 215 amino acids of cytochrome b. The mutation was heteroplasmic and was present in 87% of skeletal muscle and in a low percentage (0.7%) of blood. The mutation was also present in several other tissues, including hair roots, indicating that it must have arisen either very early in embryogenesis, before separation of the primary germ layers, or in the maternal germline. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6093035+11047755+8910895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In cells from a patient with parkinsonism and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS; <a href="/entry/540000">540000</a>) who harbored a 4-bp deletion in the MTCYB gene, <a href="#42" class="mim-tip-reference" title="Rana, M., de Coo, I., Diaz, F., Smeets, H., Moraes, C. T. <strong>An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production.</strong> Ann. Neurol. 48: 774-781, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11079541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11079541</a>]" pmid="11079541">Rana et al. (2000)</a> found defective synthesis of the protein, defective oxidative phosphorylation, defective complex III synthesis and activity, and increased hydrogen peroxide production. In the patient, CSF lactate was 10-fold higher than in serum, which may indicate accumulation of the mutation in the CNS. <a href="#42" class="mim-tip-reference" title="Rana, M., de Coo, I., Diaz, F., Smeets, H., Moraes, C. T. <strong>An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production.</strong> Ann. Neurol. 48: 774-781, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11079541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11079541</a>]" pmid="11079541">Rana et al. (2000)</a> suggested that the 4-bp deletion may increase reactive oxygen species and contribute to a variable phenotype via a mechanism different from reduced energy production. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11079541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Legros, F., Chatzoglou, E., Frachon, P., de Baulny, H. O., Laforet, P., Jardel, C., Godinot, C., Lombes, A. <strong>Functional characterization of novel mutations in the human cytochrome b gene.</strong> Europ. J. Hum. Genet. 9: 510-518, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11464242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11464242</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11464242">Legros et al. (2001)</a> analyzed the MTCYB gene in 21 patients with a mitochondrial disease (a group of 7 patients had an isolated complex III defect and a group of 14 patients had a mitochondrial disorder without an isolated complex III defect) and 146 healthy adult control subjects. Gene sequencing was used in the patients, whereas DGGE was performed in the control group. Altogether, 38 variations in the MTCYB gene sequence were identified in the patients and in the control population. The functional relevance of the sequence variations were evaluated using indirect criteria (such as the nature of the mutation, its frequency in controls, and the phylogenetic conservation of the mutated amino acid) and enzymologic and Western blot analysis of complex III. Two original deleterious mutations were found in the group of 7 patients with overt complex III defect. Both mutations (15150G-A; <a href="#0008">516020.0008</a> and 15197T-C; <a href="#0009">516020.0009</a>) were heteroplasmic and restricted to muscle tissue and both patients had an isolated intolerance to exercise from their late childhood. Spectrophotometric analysis of the respiratory chain showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. The findings underlined the pathogenic relevance of the 2 heteroplasmic mutations and further confirmed that cytochrome b alterations cause isolated complex III defect in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11464242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Andreu et al. (<a href="#3" class="mim-tip-reference" title="Andreu, A. L., Bruno, C., Shanske, S., Shtilbans, A., Hirano, M., Krishna, S., Hayward, L., Systrom, D. S., Brown, R. H., Jr., DiMauro, S. <strong>Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy.</strong> Neurology 51: 1444-1447, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9818877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9818877</a>] [<a href="https://doi.org/10.1212/wnl.51.5.1444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9818877">1998</a>, <a href="#2" class="mim-tip-reference" title="Andreu, A. L., Bruno, C., Dunne, T. C., Tanji, K., Shanske, S., Sue, C. M., Krishna, S., Hadjigeorgiou, G. M., Shtilbans, A., Bonilla, E., DiMauro, S. <strong>A nonsense mutation (G15059A) in the cytochrome b gene in a patient with exercise intolerance and myoglobinuria.</strong> Ann. Neurol. 45: 127-130, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9894887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9894887</a>] [<a href="https://doi.org/10.1002/1531-8249(199901)45:1<127::aid-art20>3.0.co;2-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9894887">1999</a>) noted that mutations in the MTCYB gene are often sporadic and can arise during embryogenesis, affecting a limited number of cells and resulting in tissue-specific phenotypes. <a href="#4" class="mim-tip-reference" title="Andreu, A. L., Checcarelli, N., Iwata, S., Shanske, S., DiMauro, S. <strong>A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy.</strong> Pediat. Res. 48: 311-314, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10960495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10960495</a>] [<a href="https://doi.org/10.1203/00006450-200009000-00008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10960495">Andreu et al. (2000)</a> identified a point mutation in the MTCYB gene (<a href="#0011">516020.0011</a>) that was associated with histiocytoid cardiomyopathy (<a href="/entry/500000">500000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10960495+9818877+9894887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Fliss, M. S., Usadel, H., Caballero, O. L., Wu, L., Buta, M. R., Eleff, S. M., Jen, J., Sidransky, D. <strong>Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.</strong> Science 287: 2017-2019, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720328</a>] [<a href="https://doi.org/10.1126/science.287.5460.2017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720328">Fliss et al. (2000)</a> identified a somatic 21-bp deletion in the MTCYB gene in tumor tissue from a patient with bladder cancer (<a href="/entry/109800">109800</a>). <a href="#14" class="mim-tip-reference" title="Dasgupta, S., Hoque, M. O., Upadhyay, S., Sidransky, D. <strong>Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer.</strong> Cancer Res. 68: 700-706, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245469</a>] [<a href="https://doi.org/10.1158/0008-5472.CAN-07-5532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18245469">Dasgupta et al. (2008)</a> found that overexpression of the 21-bp deletion identified by <a href="#18" class="mim-tip-reference" title="Fliss, M. S., Usadel, H., Caballero, O. L., Wu, L., Buta, M. R., Eleff, S. M., Jen, J., Sidransky, D. <strong>Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.</strong> Science 287: 2017-2019, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720328</a>] [<a href="https://doi.org/10.1126/science.287.5460.2017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720328">Fliss et al. (2000)</a> in murine bladder cancer cells resulted in increased tumor growth and an invasive phenotype in vitro and after injection into mice. Increased tumor growth was associated with shifts toward glycolysis and production of reactive oxygen species (ROS). Rapid cell cycle progression was associated with upregulation of the NFKB (<a href="/entry/164011">164011</a>) signaling pathway, and inhibition of ROS or NFKB diminished tumor growth in vitro. Transfection of the 21-bp deletion into human uroepithelial cells resulted in similar effects. The findings suggested that mitochondrial mutations may contribute to tumor growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18245469+10720328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>14 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/516020" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=516020[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, LHON15257A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs41518645 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs41518645;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs41518645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs41518645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010312 OR RCV000855257" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010312, RCV000855257" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010312...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This allele changes the highly conserved aspartate at amino acid 171 to an asparagine (D171N). This mutation is located in a region of approximately 20 conserved amino acids that are adjacent to an invariant histidine residue (His-183) that is involved in ligating the low potential b-566 heme (<a href="#9" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C. <strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong> Genetics 130: 163-173, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>] [<a href="https://doi.org/10.1093/genetics/130.1.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1732158">Brown et al., 1992</a>). This allele displays characteristics of both primary and secondary LHON mutations and hence may significantly contribute to the disease process. In most, but not all cases, the MTCYB*LHON15257A allele has been associated with the primary LHON mutation MTND6*LHON14484A and the secondary mutation MTND5*LHON13708A. Individuals harboring this mtDNA haplotype may also harbor the allele MTCYB*LHON15812A, and the MTCYB*LHON15257A allele has been found in association with the MTND2*LHON5244A mutation in 1 case. Overall, individuals carrying the MTCYB*LHON15257A variant make up approximately 9% of LHON patients, but the mutation is also seen in 0.3% of population controls. Families with this variant together with MTND6*LHON14484A have between 27 and 80% of maternal relatives affected, of which between 75 and 100% are males. Approximately 28% of affected individuals experience visual recovery (<a href="#8" class="mim-tip-reference" title="Brown, M. D., Lott, M. T., Voljavec, A. S., Torroni, A., Wallace, D. C. <strong>Mitochondrial DNA cytochrome b mutations associated with Leber's hereditary optic neuropathy and evidence for deleterious interactions between mutations. (Abstract)</strong> Am. J. Hum. Genet. 49 (suppl.): 973, 1991."None>Brown et al., 1991</a>; <a href="#9" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C. <strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong> Genetics 130: 163-173, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>] [<a href="https://doi.org/10.1093/genetics/130.1.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1732158">Brown et al., 1992</a>; <a href="#23" class="mim-tip-reference" title="Heher, K. L., Johns, D. R. <strong>A maculopathy associated with the 15257 mitochondrial DNA mutation.</strong> Arch. Ophthal. 111: 1495-1499, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8240104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8240104</a>] [<a href="https://doi.org/10.1001/archopht.1993.01090110061024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8240104">Heher and Johns, 1993</a>; <a href="#24" class="mim-tip-reference" title="Huoponen, K., Lamminen, T., Juvonen, V., Aula, P., Nikoskelainen, E., Savontaus, J. L. <strong>The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy.</strong> Hum. Genet. 92: 379-384, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7901141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7901141</a>] [<a href="https://doi.org/10.1007/BF01247339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7901141">Huoponen et al., 1993</a>; <a href="#25" class="mim-tip-reference" title="Johns, D. R., Neufeld, M. J. <strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong> Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1764087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1764087</a>] [<a href="https://doi.org/10.1016/0006-291x(91)92088-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1764087">Johns and Neufeld, 1991</a>; <a href="#26" class="mim-tip-reference" title="Johns, D. R., Smith, K. H., Savino, P. J., Miller, N. R. <strong>Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation.</strong> Ophthalmology 100: 981-986, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8321540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8321540</a>] [<a href="https://doi.org/10.1016/s0161-6420(93)31527-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8321540">Johns et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8321540+7901141+1764087+8240104+1732158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Mackey, D. A., Oostra, R.-J., Rosenberg, T., Nikoskelainen, E., Bronte-Stewart, J., Poulton, J., Harding, A. E., Govan, G., Bolhuis, P. A., Norby, S., Bleeker-Wagemakers, E. M., Savontaus, M.-L., Chan, C., Howell, N. <strong>Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. (Letter)</strong> Am. J. Hum. Genet. 59: 481-485, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755941</a>]" pmid="8755941">Mackey et al. (1996)</a> surveyed 159 families of northern European extraction with at least 1 case of LHON. In 97% of these families, 1 of the 3 previously identified, so-called primary mutations (3460, 11778, and 14484) were found. In no instance was the 15257 mutation found, prompting <a href="#31" class="mim-tip-reference" title="Mackey, D. A., Oostra, R.-J., Rosenberg, T., Nikoskelainen, E., Bronte-Stewart, J., Poulton, J., Harding, A. E., Govan, G., Bolhuis, P. A., Norby, S., Bleeker-Wagemakers, E. M., Savontaus, M.-L., Chan, C., Howell, N. <strong>Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. (Letter)</strong> Am. J. Hum. Genet. 59: 481-485, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755941</a>]" pmid="8755941">Mackey et al. (1996)</a> to suggest that it is not a primary mutation causing LHON. They admitted that it might represent a primary causative mutation with penetrance sufficiently high to produce a clear-cut, multigenerational pattern of maternal inheritance. They excluded single cases of LHON from their study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, LHON15812A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs200336777 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200336777;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs200336777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs200336777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010313 OR RCV000855379" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010313, RCV000855379" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010313...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This allele converts the moderately conserved aliphatic amino acid (either alanine, valine, or isoleucine) at 356 to a methionine (V356M). This is a secondary LHON mutation which is regularly found associated with the additional LHON mutations: MTND5*LHON13708A, MTND6*LHON14484A, and MTCYB*LHON15257A. While the mutation does not cause LHON, it may increase the probability of phenotypic expression (<a href="#8" class="mim-tip-reference" title="Brown, M. D., Lott, M. T., Voljavec, A. S., Torroni, A., Wallace, D. C. <strong>Mitochondrial DNA cytochrome b mutations associated with Leber's hereditary optic neuropathy and evidence for deleterious interactions between mutations. (Abstract)</strong> Am. J. Hum. Genet. 49 (suppl.): 973, 1991."None>Brown et al., 1991</a>; <a href="#9" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C. <strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong> Genetics 130: 163-173, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>] [<a href="https://doi.org/10.1093/genetics/130.1.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1732158">Brown et al., 1992</a>; <a href="#25" class="mim-tip-reference" title="Johns, D. R., Neufeld, M. J. <strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong> Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1764087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1764087</a>] [<a href="https://doi.org/10.1016/0006-291x(91)92088-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1764087">Johns and Neufeld, 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1764087+1732158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 14985G-A, ARG80HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207459995 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207459995;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207459995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207459995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010314 OR RCV000855200" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010314, RCV000855200" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010314...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Early on, <a href="#51" class="mim-tip-reference" title="Warburg, O. <strong>On the origin of cancer cells.</strong> Science 123: 309-314, 1956.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13298683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13298683</a>] [<a href="https://doi.org/10.1126/science.123.3191.309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13298683">Warburg (1956)</a> suggested that alterations of oxidative phosphorylation in tumor cells play a causative role in cancerous growth. Interest in mitochondria with regard to neoplasia has revived, largely because of their role in apoptosis and other aspects of tumor biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generated in this organelle, coupled with a low level of DNA repair. In a colorectal cancer, <a href="#41" class="mim-tip-reference" title="Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B. <strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong> Nature Genet. 20: 291-293, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806551</a>] [<a href="https://doi.org/10.1038/3108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9806551">Polyak et al. (1998)</a> found 3 somatic mutations in the mitochondrial genome. Two occurred in the MTCYB gene: a 14985G-A change leading to an arg80-to-his substitution; and a 15572T-C transition, leading to a phe276-to-leu substitution (<a href="#0004">516020.0004</a>). The third mutation occurred in the MTCO1 gene; see <a href="/entry/516040#0002">516040.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9806551+13298683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15572T-C, PHE276LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207459996 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207459996;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207459996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207459996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010315 OR RCV002247304" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010315, RCV002247304" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010315...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0003">516020.0003</a> and <a href="#41" class="mim-tip-reference" title="Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B. <strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong> Nature Genet. 20: 291-293, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806551</a>] [<a href="https://doi.org/10.1038/3108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9806551">Polyak et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9806551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15615G-A, GLY290ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207459997 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207459997;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207459997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207459997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010316 OR RCV000855331" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010316, RCV000855331" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010316...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Bouzidi, M. F., Schagger, H., Collombet, J. M., Carrier, H., Flocard, F., Quard, S., Mousson, B., Godinot, C. <strong>Decreased expression of ubiquinol-cytochrome c reductase subunits in patients exhibiting mitochondrial myopathy with progressive exercise intolerance.</strong> Neuromusc. Disord. 3: 599-604, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8186719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8186719</a>] [<a href="https://doi.org/10.1016/0960-8966(93)90123-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8186719">Bouzidi et al. (1993)</a> found low activity of respiratory chain complex III in muscle from a 25-year-old man with exercise intolerance in whom <a href="#16" class="mim-tip-reference" title="Dumoulin, R., Sagnol, I., Ferlin, T., Bozon, D., Stepien, G., Mousson, B. <strong>A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance.</strong> Molec. Cell Probes 10: 389-391, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8910895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8910895</a>] [<a href="https://doi.org/10.1006/mcpr.1996.0053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8910895">Dumoulin et al. (1996)</a> later identified a missense mutation, 15615G-A, in the mitochondrial cytochrome b gene, the only mtDNA encoded subunit of complex III. The findings in this patient were reviewed by <a href="#5" class="mim-tip-reference" title="Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S. <strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong> New Eng. J. Med. 341: 1037-1044, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502593</a>] [<a href="https://doi.org/10.1056/NEJM199909303411404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502593">Andreu et al. (1999)</a> as part of a series of 9 cases, 5 of their own and 4 reported by others. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10502593+8910895+8186719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 14846G-A, GLY34SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207459998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207459998;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207459998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207459998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010317 OR RCV000855169 OR RCV002265553 OR RCV004791206" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010317, RCV000855169, RCV002265553, RCV004791206" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010317...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of the 5 patients with exercise intolerance due to mutation in the cytochrome b gene of mitochondrial DNA identified by <a href="#5" class="mim-tip-reference" title="Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S. <strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong> New Eng. J. Med. 341: 1037-1044, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502593</a>] [<a href="https://doi.org/10.1056/NEJM199909303411404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502593">Andreu et al. (1999)</a> was a 52-year-old woman who had had exercise intolerance since childhood with muscle weakness and myopathy on electromyography and hyperlactic acidemia. The patient showed 'ragged-red fibers' (22%) on muscle biopsy. The nucleotide substitution resulted in a gly34-to-ser amino acid substitution. Lactic acidosis in the resting state was found in 4 of the 5 patients studied by <a href="#5" class="mim-tip-reference" title="Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S. <strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong> New Eng. J. Med. 341: 1037-1044, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502593</a>] [<a href="https://doi.org/10.1056/NEJM199909303411404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502593">Andreu et al. (1999)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ENCEPHALOMYOPATHY, MITOCHONDRIAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15242G-A, GLY166TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207459999 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207459999;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207459999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207459999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010318 OR RCV000855252 OR RCV004691092" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010318, RCV000855252, RCV004691092" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010318...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#27" class="mim-tip-reference" title="Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G. <strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong> Am. J. Hum. Genet. 67: 1400-1410, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11047755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11047755</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11047755[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11047755">Keightley et al. (2000)</a> presented observations on a 34-year-old woman followed for 17 years. She had a history of progressive exercise intolerance and lactic acidosis starting at approximately 9 years of age. By age 19 years she had clear evidence of encephalopathy, with emotional lability, seizures, abnormal EEG, intermittent visual hallucinations, and depression. The authors identified a stop mutation, 15242G-A, predicting a gly166-to-ter truncation of the protein with loss of 215 amino acids, representing 57% of the C terminus of cytochrome b. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11047755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15150G-A, TRP135TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460000 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460000;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010319 OR RCV000855232 OR RCV002247305 OR RCV004791207" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010319, RCV000855232, RCV002247305, RCV004791207" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010319...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with isolated intolerance to exercise from late childhood, <a href="#29" class="mim-tip-reference" title="Legros, F., Chatzoglou, E., Frachon, P., de Baulny, H. O., Laforet, P., Jardel, C., Godinot, C., Lombes, A. <strong>Functional characterization of novel mutations in the human cytochrome b gene.</strong> Europ. J. Hum. Genet. 9: 510-518, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11464242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11464242</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11464242">Legros et al. (2001)</a> identified a nonsense mutation, 15150G-A, predicting a trp135-to-ter truncation of the protein. The family history was negative. The mutation was restricted to muscle tissue where it represented 60% of the mtDNA molecules. The mutation was absent in a control population of 146 healthy adults. Spectrophotometric analysis showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. Western blot analysis of complex III in muscle showed undetectable cytochrome b protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11464242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15197T-C, SER151PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460001 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460001;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010320 OR RCV004691093" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010320, RCV004691093" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010320...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with isolated intolerance to exercise from late childhood, <a href="#29" class="mim-tip-reference" title="Legros, F., Chatzoglou, E., Frachon, P., de Baulny, H. O., Laforet, P., Jardel, C., Godinot, C., Lombes, A. <strong>Functional characterization of novel mutations in the human cytochrome b gene.</strong> Europ. J. Hum. Genet. 9: 510-518, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11464242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11464242</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11464242">Legros et al. (2001)</a> identified a missense mutation, 15197T-C, resulting in a ser151-to-pro amino acid substitution. The serine at position 151 was highly conserved and the mutation constituted an important modification in the physicochemical properties of the amino acid. The family history was negative. The mutation was restricted to muscle tissue where it represented 80% of the mtDNA molecules. The mutation was absent in a control population of 146 healthy adults. Spectrophotometric analysis showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. Western blot analysis of complex III in muscle showed a reduced amount of cytochrome b protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11464242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MULTISYSTEM DISORDER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15579A-G, TYR278CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460002;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010321 OR RCV000855325 OR RCV002247306 OR RCV003153301" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010321, RCV000855325, RCV002247306, RCV003153301" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010321...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Whereas most mutations in the MTCYB gene had been reported to cause a homogeneous phenotype of pure exercise intolerance, <a href="#53" class="mim-tip-reference" title="Wibrand, F., Ravn, K., Schwartz, M., Rosenberg, T., Horn, N., Vissing, J. <strong>Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene.</strong> Ann. Neurol. 50: 540-543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601507</a>] [<a href="https://doi.org/10.1002/ana.1224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11601507">Wibrand et al. (2001)</a> described a 15579A-G mutation associated with a selective decrease of muscle complex III activity in a patient who, besides severe exercise intolerance, also had multisystem manifestations (deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, epilepsy). The 15579A-G mutation was heteroplasmic in muscle (88%) and leukocytes (15%), and changed a highly conserved tyrosine to cysteine at amino acid position 278. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11601507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CARDIOMYOPATHY, INFANTILE HISTIOCYTOID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15498G-A, GLY251ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460003;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010322 OR RCV000855308" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010322, RCV000855308" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010322...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl who died of cardiac arrest at the age of 4 weeks and was found to have typical pathologic features of histiocytoid cardiomyopathy (<a href="/entry/500000">500000</a>), <a href="#4" class="mim-tip-reference" title="Andreu, A. L., Checcarelli, N., Iwata, S., Shanske, S., DiMauro, S. <strong>A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy.</strong> Pediat. Res. 48: 311-314, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10960495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10960495</a>] [<a href="https://doi.org/10.1203/00006450-200009000-00008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10960495">Andreu et al. (2000)</a> identified a point mutation in the MTCYB gene, a G-to-A transition at nucleotide 15498, resulting in a gly251-to-asp substitution. The mutation, which was heteroplasmic and fulfilled all accepted criteria for pathogenicity, was thought to impair the function of the holoenzyme as deduced from its effects on the crystal structure of ubiquinol cytochrome c oxidoreductase. The infant showed involvement of other organs, including liver (hepatic steatosis) and kidney (acute tubular necrosis). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10960495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 14849T-C, SER35PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460004 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460004;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010323 OR RCV000855170 OR RCV002260587" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010323, RCV000855170, RCV002260587" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010323...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#46" class="mim-tip-reference" title="Schuelke, M., Krude, H., Finckh, B., Mayatepek, E., Janssen, A., Schmelz, M., Trefz, F., Trijbels, F., Smeitink, J. <strong>Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.</strong> Ann. Neurol. 51: 388-392, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891837</a>] [<a href="https://doi.org/10.1002/ana.10151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891837">Schuelke et al. (2002)</a> reported a patient with neurologic symptoms starting in infancy and manifesting as hypotonia, retarded language and motor development, dysdiadochokinesia, gait ataxia, small head circumference, cerebellar hypoplasia, and exercise intolerance. In addition, he had hypertrophic cardiomyopathy, retinitis pigmentosa, and features of septooptic dysplasia; the latter 2 symptoms had not previously been described in association with complex III deficiency. The patient was found to have a 14849T-C mutation in the MTCYB gene, resulting in a substitution of a highly conserved serine for proline at position 35. The mutation was heteroplasmic in muscle (69%) and fibroblasts (12%), although residual complex III activity was the same in both tissues (70%). The authors suggested that the mutation may lead to increased reactive oxygen species, which may play a role in the pathogenic findings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PARKINSONISM/MELAS OVERLAP SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 4-BP DEL, 14787TTAA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs207460005 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs207460005;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs207460005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs207460005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010324 OR RCV003985259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010324, RCV003985259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010324...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with diminished activity of complex III of the mitochondrial respiratory chain, <a href="#15" class="mim-tip-reference" title="De Coo, I. F. M., Renier, W. O., Ruitenbeek, W., Ter Laak, H. J., Bakker, M., Schagger, H., Van Oost, B. A., Smeets, H. J. M. <strong>A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.</strong> Ann. Neurol. 45: 130-133, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9894888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9894888</a>] [<a href="https://doi.org/10.1002/1531-8249(199901)45:1<130::aid-art21>3.3.co;2-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9894888">De Coo et al. (1999)</a> identified a heteroplasmic 4-bp deletion in a highly conserved portion of the cytochrome b gene. The deletion was predicted to lead to a truncated protein. The patient had a severe progressive disorder beginning at age 6 years with difficulty in fine motor coordination and concentration. He later developed behavioral changes, parkinsonism, myoclonus, extensor plantar responses, and cerebral infarcts. More than 95% of the mtDNA in muscle was mutated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9894888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 OBESITY, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCYB, 15497G-A, GLY251SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199951903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199951903;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199951903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199951903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000022894 OR RCV000434000 OR RCV000855307" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022894, RCV000434000, RCV000855307" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022894...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#37" class="mim-tip-reference" title="Okura, T., Koda, M., Ando, F., Niino, N., Tanaka, M., Shimokata, H. <strong>Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population.</strong> Hum. Genet. 113: 432-436, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12905068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12905068</a>] [<a href="https://doi.org/10.1007/s00439-003-0983-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12905068">Okura et al. (2003)</a> examined the possible relationship between the Mt15497G-A polymorphism and obesity (<a href="/entry/601665">601665</a>) by studying middle-aged and elderly Japanese individuals (825 women and 906 men). After adjusting for age and smoking, they found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intraabdominal fat, and triglycerides were significantly greater in women with the A allele compared with the G allele. For men, waist-to-hip ratio was significantly greater, and waist circumference, intraabdominal fat, and triglycerides had a trend to be significantly greater, in subjects with the A allele compared with the G allele. These data suggested that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12905068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Mitchell1976" class="mim-tip-reference" title="Mitchell, P. <strong>Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity.</strong> Biochem. Soc. Trans. 4: 399-430, 1976.">Mitchell (1976)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Anderson1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
|
|
<strong>Sequence and organization of the human mitochondrial genome.</strong>
|
|
Nature 290: 457-465, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290457a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Andreu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Bruno, C., Dunne, T. C., Tanji, K., Shanske, S., Sue, C. M., Krishna, S., Hadjigeorgiou, G. M., Shtilbans, A., Bonilla, E., DiMauro, S.
|
|
<strong>A nonsense mutation (G15059A) in the cytochrome b gene in a patient with exercise intolerance and myoglobinuria.</strong>
|
|
Ann. Neurol. 45: 127-130, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9894887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9894887</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9894887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1531-8249(199901)45:1<127::aid-art20>3.0.co;2-y" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Andreu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Bruno, C., Shanske, S., Shtilbans, A., Hirano, M., Krishna, S., Hayward, L., Systrom, D. S., Brown, R. H., Jr., DiMauro, S.
|
|
<strong>Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy.</strong>
|
|
Neurology 51: 1444-1447, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9818877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9818877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9818877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.51.5.1444" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Andreu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Checcarelli, N., Iwata, S., Shanske, S., DiMauro, S.
|
|
<strong>A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy.</strong>
|
|
Pediat. Res. 48: 311-314, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10960495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10960495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10960495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-200009000-00008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Andreu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S.
|
|
<strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong>
|
|
New Eng. J. Med. 341: 1037-1044, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199909303411404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Attardi1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
|
|
<strong>Identification and mapping of human mitochondrial genes.</strong>
|
|
Cytogenet. Cell Genet. 32: 85-98, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7140372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000131689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bouzidi1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bouzidi, M. F., Schagger, H., Collombet, J. M., Carrier, H., Flocard, F., Quard, S., Mousson, B., Godinot, C.
|
|
<strong>Decreased expression of ubiquinol-cytochrome c reductase subunits in patients exhibiting mitochondrial myopathy with progressive exercise intolerance.</strong>
|
|
Neuromusc. Disord. 3: 599-604, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8186719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8186719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8186719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0960-8966(93)90123-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Brown1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Lott, M. T., Voljavec, A. S., Torroni, A., Wallace, D. C.
|
|
<strong>Mitochondrial DNA cytochrome b mutations associated with Leber's hereditary optic neuropathy and evidence for deleterious interactions between mutations. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 973, 1991.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Brown1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C.
|
|
<strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong>
|
|
Genetics 130: 163-173, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1732158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/genetics/130.1.163" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Case1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Case, J. T., Wallace, D. C.
|
|
<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
|
|
Somat. Cell Genet. 7: 103-108, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6261411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01544751" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chomyn1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G.
|
|
<strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong>
|
|
Nature 314: 592-597, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3921850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3921850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3921850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/314592a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Crivellone1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crivellone, M. D., Wu, M., Tzagoloff, A.
|
|
<strong>Assembly of the mitochondrial membrane system. Analysis of structural mutants of the yeast coenzyme QH2-cytochrome c reductase complex..</strong>
|
|
J. Biol. Chem. 263: 14323-14333, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2844766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2844766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2844766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Darley-Usmar1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Darley-Usmar, V. M., Kennaway, N. G., Buist, N. R. M., Capaldi, R. A.
|
|
<strong>Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 5103-5106, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6308671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6308671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6308671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.80.16.5103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Dasgupta2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dasgupta, S., Hoque, M. O., Upadhyay, S., Sidransky, D.
|
|
<strong>Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer.</strong>
|
|
Cancer Res. 68: 700-706, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18245469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18245469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18245469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1158/0008-5472.CAN-07-5532" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="De Coo1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Coo, I. F. M., Renier, W. O., Ruitenbeek, W., Ter Laak, H. J., Bakker, M., Schagger, H., Van Oost, B. A., Smeets, H. J. M.
|
|
<strong>A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.</strong>
|
|
Ann. Neurol. 45: 130-133, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9894888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9894888</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9894888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1531-8249(199901)45:1<130::aid-art21>3.3.co;2-q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Dumoulin1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dumoulin, R., Sagnol, I., Ferlin, T., Bozon, D., Stepien, G., Mousson, B.
|
|
<strong>A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance.</strong>
|
|
Molec. Cell Probes 10: 389-391, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8910895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8910895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8910895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/mcpr.1996.0053" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Esposti1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Esposti, M. D., De Vries, S., Crimi, M., Ghelli, A., Patarnello, T., Meyer, A.
|
|
<strong>Mitochondrial cytochrome b: evolution and structure of the protein.</strong>
|
|
Biochim. Biophys. Acta 1143: 243-271, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8329437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8329437</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8329437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0005-2728(93)90197-n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Fliss2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fliss, M. S., Usadel, H., Caballero, O. L., Wu, L., Buta, M. R., Eleff, S. M., Jen, J., Sidransky, D.
|
|
<strong>Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.</strong>
|
|
Science 287: 2017-2019, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.287.5460.2017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Giles1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6256757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.77.11.6715" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Gonzalez-Halphen1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gonzalez-Halphen, D., Lindorfer, M. A., Capaldi, R. A.
|
|
<strong>Subunit arrangement in beef heart complex III.</strong>
|
|
Biochemistry 27: 7021-7031, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848575</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2848575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00418a053" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hatefi1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hatefi, Y.
|
|
<strong>The mitochondrial electron transport and oxidative phosphorylation system.</strong>
|
|
Annu. Rev. Biochem. 54: 1015-1069, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2862839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2862839</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2862839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.bi.54.070185.005055" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Hayes1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hayes, D. J., Lecky, B. R. F., Landon, D. N., Morgan-Hughes, J. A., Clark, J. B.
|
|
<strong>A new mitochondrial myopathy: biochemical studies revealing a deficiency in the cytochrome b-c1 complex (complex III) of the respiratory chain.</strong>
|
|
Brain 107: 1165-1177, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6095966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6095966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6095966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/107.4.1165" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Heher1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heher, K. L., Johns, D. R.
|
|
<strong>A maculopathy associated with the 15257 mitochondrial DNA mutation.</strong>
|
|
Arch. Ophthal. 111: 1495-1499, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8240104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8240104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8240104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archopht.1993.01090110061024" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Huoponen1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huoponen, K., Lamminen, T., Juvonen, V., Aula, P., Nikoskelainen, E., Savontaus, J. L.
|
|
<strong>The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy.</strong>
|
|
Hum. Genet. 92: 379-384, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7901141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7901141</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7901141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01247339" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Johns1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1764087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1764087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1764087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)92088-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Johns1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Smith, K. H., Savino, P. J., Miller, N. R.
|
|
<strong>Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation.</strong>
|
|
Ophthalmology 100: 981-986, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8321540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8321540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8321540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0161-6420(93)31527-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Keightley2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G.
|
|
<strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong>
|
|
Am. J. Hum. Genet. 67: 1400-1410, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11047755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11047755</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11047755[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11047755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/316900" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Kennaway1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kennaway, N. G., Buist, N. R., Darley-Usmar, V. M., Papadimitriou, A., Dimauro, S., Kelley, R. I., Capaldi, R. A., Blank, N. K., D'Agostino, A.
|
|
<strong>Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain.</strong>
|
|
Pediat. Res. 18: 991-999, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6093035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6093035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6093035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-198410000-00017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Legros2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Legros, F., Chatzoglou, E., Frachon, P., de Baulny, H. O., Laforet, P., Jardel, C., Godinot, C., Lombes, A.
|
|
<strong>Functional characterization of novel mutations in the human cytochrome b gene.</strong>
|
|
Europ. J. Hum. Genet. 9: 510-518, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11464242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11464242</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11464242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200678" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Linke1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Linke, P., Weiss, H.
|
|
<strong>Reconstitution of ubiquinol-cytochrome c reductase from Neurospora mitochondria with regard to subunits I and II.</strong>
|
|
Methods Enzymol. 126: 201-210, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2856127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2856127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2856127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0076-6879(86)26022-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Mackey1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mackey, D. A., Oostra, R.-J., Rosenberg, T., Nikoskelainen, E., Bronte-Stewart, J., Poulton, J., Harding, A. E., Govan, G., Bolhuis, P. A., Norby, S., Bleeker-Wagemakers, E. M., Savontaus, M.-L., Chan, C., Howell, N.
|
|
<strong>Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. (Letter)</strong>
|
|
Am. J. Hum. Genet. 59: 481-485, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Mitchell1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mitchell, P.
|
|
<strong>Possible molecular mechanisms of the proton motive function of cytochrome systems.</strong>
|
|
J. Theor. Biol. 62: 327-347, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/186667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">186667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=186667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0022-5193(76)90124-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Mitchell1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mitchell, P.
|
|
<strong>Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity.</strong>
|
|
Biochem. Soc. Trans. 4: 399-430, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/137147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">137147</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=137147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/bst0040399" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Montoya1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290465a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Morgan-Hughes1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan-Hughes, J. A., Hayes, D. J., Clark, J. B., Landon, D. N., Swash, M., Stark, R. J., Rudge, P.
|
|
<strong>Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain.</strong>
|
|
Brain 105: 553-582, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7104666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7104666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7104666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/105.3.553" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Ojala1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290470a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Okura2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okura, T., Koda, M., Ando, F., Niino, N., Tanaka, M., Shimokata, H.
|
|
<strong>Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population.</strong>
|
|
Hum. Genet. 113: 432-436, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12905068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12905068</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12905068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-003-0983-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Oliver1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6438810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01535230" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Oliver1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6955589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Oudshoorn1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oudshoorn, P., Van Steeg, H., Swinkels, B. W., Schoppink, P., Grivell, L. A.
|
|
<strong>Subunit II of yeast QH2:cytochrome-c oxidoreductase. Nucleotide sequence of the gene and features of the protein..</strong>
|
|
Europ. J. Biochem. 163: 97-103, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3028797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3028797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3028797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1432-1033.1987.tb10741.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Polyak1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong>
|
|
Nature Genet. 20: 291-293, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9806551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/3108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Rana2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rana, M., de Coo, I., Diaz, F., Smeets, H., Moraes, C. T.
|
|
<strong>An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production.</strong>
|
|
Ann. Neurol. 48: 774-781, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11079541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11079541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11079541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Rieske1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rieske, J. S.
|
|
<strong>Composition, structure, and function of complex III of the respiratory chain.</strong>
|
|
Biochim. Biophys. Acta 456: 195-247, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/788795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">788795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=788795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0304-4173(76)90012-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Saraste1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saraste, M.
|
|
<strong>Location of haem-binding sites in the mitochondrial cytochrome b.</strong>
|
|
FEBS Lett. 166: 367-372, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6363134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6363134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6363134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0014-5793(84)80114-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Schagger1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schagger, H., Link, T. A., Engel, W. D., von Jagow, G.
|
|
<strong>Isolation of the eleven protein subunits of the bc1 complex from beef heart.</strong>
|
|
Methods Enzymol. 126: 224-237, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2856130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2856130</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2856130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0076-6879(86)26024-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Schuelke2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schuelke, M., Krude, H., Finckh, B., Mayatepek, E., Janssen, A., Schmelz, M., Trefz, F., Trijbels, F., Smeitink, J.
|
|
<strong>Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.</strong>
|
|
Ann. Neurol. 51: 388-392, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.10151" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Spiro1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spiro, A. J., Moore, C. L., Prineas, J. W., Strasberg, P. M., Rapin, I.
|
|
<strong>A cytochrome-related inherited disorder of the nervous system and muscle.</strong>
|
|
Arch. Neurol. 23: 103-112, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5430330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5430330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5430330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1970.00480260009002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Tzagoloff1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tzagoloff, A., Wu, M. A., Crivellone, M.
|
|
<strong>Assembly of the mitochondrial membrane system. Characterization of COR1, the structural gene for the 44-kilodalton core protein of yeast coenzyme QH2-cytochrome c reductase.</strong>
|
|
J. Biol. Chem. 261: 17163-17169, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3023384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3023384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3023384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Wallace1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Wallace1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3518425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Warburg1956" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warburg, O.
|
|
<strong>On the origin of cancer cells.</strong>
|
|
Science 123: 309-314, 1956.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13298683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13298683</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13298683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.123.3191.309" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Weiss1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weiss, H., Linke, P., Haiker, H., Leonard, K.
|
|
<strong>Structure and function of the mitochondrial ubiquinol: cytochrome c reductase and NADH: ubiquinone reductase.</strong>
|
|
Biochem. Soc. Trans. 15: 100-102, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3030833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3030833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3030833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/bst0150100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Wibrand2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wibrand, F., Ravn, K., Schwartz, M., Rosenberg, T., Horn, N., Vissing, J.
|
|
<strong>Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene.</strong>
|
|
Ann. Neurol. 50: 540-543, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11601507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.1224" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Wikstrom1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wikstrom, M., Krab, K., Saraste, M.
|
|
<strong>Proton-translocating cytochrome complexes.</strong>
|
|
Annu. Rev. Biochem. 50: 623-655, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6267990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6267990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6267990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.bi.50.070181.003203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Wikstrom1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wikstrom, M., Krab, K.
|
|
<strong>The semiquinone cycle. A hypothesis of electron transfer and proton translocation in cytochrome bc-type complexes.</strong>
|
|
J. Bioenerg. Biomembr. 18: 181-193, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3015895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3015895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3015895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00743463" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 10/23/2008
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick - updated : 10/1/2003<br>Cassandra L. Kniffin - updated : 9/18/2003<br>Cassandra L. Kniffin - updated : 8/13/2002<br>Cassandra L. Kniffin - updated : 7/8/2002<br>Victor A. McKusick - updated : 4/23/2002<br>Victor A. McKusick - updated : 12/13/2001<br>Michael B. Petersen - updated : 11/28/2001<br>Victor A. McKusick - updated : 12/13/2000<br>Victor A. McKusick - updated : 10/6/1999<br>Victor A. McKusick - updated : 6/17/1998<br>Douglas C. Wallace - updated : 4/6/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 3/2/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 05/05/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 05/04/2022<br>carol : 03/18/2022<br>carol : 07/28/2015<br>terry : 5/24/2011<br>terry : 3/23/2011<br>terry : 3/23/2011<br>terry : 3/23/2011<br>terry : 3/22/2011<br>ckniffin : 11/24/2010<br>carol : 1/19/2010<br>wwang : 10/24/2008<br>ckniffin : 10/23/2008<br>ckniffin : 10/23/2008<br>terry : 4/6/2005<br>alopez : 10/6/2003<br>terry : 10/1/2003<br>carol : 10/1/2003<br>ckniffin : 9/18/2003<br>ckniffin : 1/3/2003<br>carol : 8/22/2002<br>ckniffin : 8/13/2002<br>carol : 8/9/2002<br>ckniffin : 8/9/2002<br>carol : 8/9/2002<br>ckniffin : 7/8/2002<br>terry : 6/27/2002<br>mgross : 4/26/2002<br>terry : 4/23/2002<br>alopez : 12/13/2001<br>cwells : 12/5/2001<br>cwells : 11/28/2001<br>terry : 1/19/2001<br>mcapotos : 1/9/2001<br>mcapotos : 12/27/2000<br>terry : 12/13/2000<br>terry : 11/24/1999<br>carol : 10/6/1999<br>jlewis : 6/23/1999<br>jlewis : 6/23/1999<br>jlewis : 6/22/1999<br>jlewis : 6/21/1999<br>carol : 2/24/1999<br>terry : 6/18/1998<br>terry : 6/17/1998<br>dholmes : 5/11/1998<br>dholmes : 5/11/1998<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>mimadm : 5/17/1994<br>pfoster : 5/12/1994<br>carol : 2/28/1994<br>carol : 5/26/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 516020
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CYTOCHROME b OF COMPLEX III; MTCYB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
COMPLEX III, CYTOCHROME b SUBUNIT<br />
|
|
UBIQUINONE-CYTOCHROME c OXIDOREDUCTASE, CYTOCHROME b SUBUNIT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: MT-CYB</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 267044007, 447292006, 58610003;
|
|
|
|
|
|
<strong>ICD10CM:</strong> H47.22;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cytochrome b (MTCYB) is the only mitochondrial DNA (mtDNA) encoded subunit of respiratory Complex III (ubiquinol:ferrocytochrome c oxidoreductase, or cytochrome bc1, complex, EC 1.10.2.2). Complex III is located within the mitochondrial inner membrane and is the second enzyme in the electron transport chain of mitochondrial oxidative phosphorylation. It catalyzes the transfer of electrons from ubiquinol (reduced Coenzyme Q10) to cytochrome c and utilizes the energy to translocate protons from inside the mitochondrial inner membrane to outside. Bovine Complex III has been resolved into 11 polypeptides by SDS-polyacrylamide gels (PAGE), designated I-XI (Schagger et al., 1986; Gonzalez-Halphen et al., 1988). These subunits include core proteins I and II, cytochrome b (subunit III), cytochrome c1 (subunit IV), the Rieske iron-sulfur protein (subunit V), and several smaller polypeptides. Subunits III, IV, and V are the major redox proteins in the complex and are present in the molar ratio 2:1:1 (Rieske, 1976). The core proteins I and II are essential for the assembly and proper association of the redox centers in Complex III, though they do not contain redox centers (Linke and Weiss, 1986; Crivellone et al., 1988; Oudshoorn et al., 1987; Tzagoloff et al., 1986). </p><p>MTCYB is a highly evolutionarily conserved, hydrophobic protein containing 8 or 9 transmembrane domains and 2 heme groups. The 2 hemes differ in redox potential and difference spectra and have been designated b-562--the high potential heme, and b-566--the low potential heme (Esposti et al., 1993; Wikstrom et al., 1981; Saraste, 1984). Cytochrome b together with core proteins I and II comprise the central components of Complex III. The Rieske iron-sulfur protein is on the cytoplasmic side of the inner membrane and accepts electrons from MTCYB (Gonzalez-Halphen et al., 1988). The electrons are then transferred to cytochrome c1 which contains 1 membrane-spanning domain, a covalently bound heme, and is also located on the outside of the mitochondrial inner membrane. Cytochrome c1 transfers electrons to cytochrome c (Weiss et al., 1987). </p><p>The mechanism by which proton translocation is linked to electron transport has been studied intensively for Complex III. Two important models are the proton-motive ubiquinone (Q) cycle and the b-cycle (Mitchell, 1976; Hatefi, 1985). Both models link proton translocation and electron transfer through ubiquinone redox intermediates (Hatefi, 1985; Wikstrom and Krab, 1986). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>MTCYB is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 14747 and 15887 (Anderson et al., 1981; Wallace et al., 1994). It is maternally inherited along with the mtDNA (Giles et al., 1980; Case and Wallace, 1981). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The MTCYB gene encompasses 1140 nps of mtDNA and encodes a single polypeptide without introns. The mRNA has a 4-np, 5-prime noncoding region followed by the AUG start codon, and ends with the U of the UAA termination codon (Anderson et al., 1981; Ojala et al., 1981; Montoya et al., 1981; Wallace et al., 1994). It is transcribed as a part of the polycistronic H-strand transcript, flanked by the tRNAGlu and tRNAThr transcripts. These tRNAs are cleaved out at the transcript freeing transcript 11, the MTCYB mRNA. The mRNA is then polyadenylated completing the termination codon (Anderson et al., 1981; Ojala et al., 1981: Attardi et al., 1982). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The predicted molecular weight (MW) of MTCYB is 42.7 kD (Anderson et al., 1981; Wallace et al., 1994). However, its high hydrophobicity results in variable migration on SDS-PAGE with an altered apparent molecular weight. Using Tris-glycine buffer it migrates at approximately 27.5 kD (Oliver et al., 1984; Oliver and Wallace, 1982; Wallace et al., 1986), whereas in urea-phosphate buffer it migrates at about 29 kD (Chomyn et al., 1985). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Restriction site polymorphisms have been identified at the following nucleotide position for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, Anderson et al., 1981): Alu I: +14899, +15245, +15437, +15606, -15776; Ava II: +15487, +15591, +15882; Dde I: +14773, +14923, -15073, -15238, -15250, +15434, +15660, +15727, +15751/15754; Hae II: -14858, -15002; Hae III: +14749, +14899, -15047, -15073, -15172, +15431, +15520, +15595, -15883; Hha I: -14859, -15003; HincII: +14648/15765; HinfI: +15005, -15234, -15375, -15723; Mbo I: +14749, -14869, -15060, +15195/15221, +15235, +15397, -15591, +15790/16373; Msp I: +15485; Rsa I: +15346, +15412, -15812, +15872; Taq I: -14956, +15549, +15861; Xho I: -15068 (Wallace et al., 1994). </p><p>MTCYB has phenotypically relevant alleles that contribute to Leber hereditary optic neuropathy (LHON; 535000), including MTCYB*LHON15257A (516020.0001) and MTCYB*LHON15812A (516020.0002).</p><p>Spiro et al. (1970) described a 46-year-old man and his 16-year-old son with progressive ataxia, predominantly proximal muscle weakness, areflexia, extensor plantar responses, dementia, and concomitant nonspecific myopathic and neuropathic changes in muscle. Studies of muscle mitochondria showed very loose coupling of oxidative phosphorylation and marked reduction in cytochrome b content, representing a defect in complex III. Morgan-Hughes et al. (1982) reported a patient with a defect at the cytochrome b level in the mitochondrial respiratory chain. The patient had onset of myoclonus followed by generalized weakness, ataxia, and mental confusion. Patients with complex III deficiency reported by Darley-Usmar et al. (1983) and Hayes et al. (1984) had combinations of muscular weakness, ataxia, exercise intolerance, and ocular myopathy. Most problems were initially noted in childhood and worsened with age. </p><p>Andreu et al. (1999) described 5 new patients with exercise intolerance in whom they identified mutations in the MTCYB gene, and reviewed the characteristics of 4 patients previously identified. They concluded that there is a sporadic form of mitochondrial myopathy in which exercise intolerance is the predominant symptom. Each of the mutations in the MTCYB gene impaired the enzymatic function of the cytochrome b protein. In these patients, the clinical manifestations included progressive exercise intolerance, proximal limb weakness, and in some cases attacks of myoglobinuria. There was no maternal inheritance and there were no mutations in tissues other than muscle. The absence of these findings suggested that the disorder is due to somatic mutations in myogenic stem cells after germ-layer differentiation. All of the point mutations involved the substitution of adenine for guanine, but all were in different locations. </p><p>Keightley et al. (2000) stated that the report by Dumoulin et al. (1996) was the first instance of isolated complex III deficiency in which mutation in the cytochrome b gene was shown to be pathogenic, after which 12 additional pathogenic mutations in this gene were described in various studies. Most of the patients presented with the predominant feature of severe exercise intolerance, sometimes including muscle weakness and/or myoglobinuria. Keightley et al. (2000) reinvestigated a young woman, originally reported by Kennaway et al. (1984), who presented with exercise intolerance and lactic acidosis associated with severe deficiency of complex III and who responded to therapy with menadione and ascorbate. She gradually developed symptoms of a mitochondrial encephalomyopathy. Immunocytochemistry of serial sections of muscle showed a mosaic of fibers that reacted poorly with antibodies to subunits of complex III but reacted normally with antibodies to subunits of complex I, II, or IV, suggesting a mutation of mtDNA. This experience demonstrated the diagnostic value of immunocytochemistry in identifying specific respiratory-chain deficiencies and, potentially, distinguishing between nuclear- and mtDNA-encoded defects. Keightley et al. (2000) demonstrated a stop codon mutation, 15242G-A (516020.0007), in the mtDNA-encoded cytochrome b gene, resulting in loss of the last 215 amino acids of cytochrome b. The mutation was heteroplasmic and was present in 87% of skeletal muscle and in a low percentage (0.7%) of blood. The mutation was also present in several other tissues, including hair roots, indicating that it must have arisen either very early in embryogenesis, before separation of the primary germ layers, or in the maternal germline. </p><p>In cells from a patient with parkinsonism and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS; 540000) who harbored a 4-bp deletion in the MTCYB gene, Rana et al. (2000) found defective synthesis of the protein, defective oxidative phosphorylation, defective complex III synthesis and activity, and increased hydrogen peroxide production. In the patient, CSF lactate was 10-fold higher than in serum, which may indicate accumulation of the mutation in the CNS. Rana et al. (2000) suggested that the 4-bp deletion may increase reactive oxygen species and contribute to a variable phenotype via a mechanism different from reduced energy production. </p><p>Legros et al. (2001) analyzed the MTCYB gene in 21 patients with a mitochondrial disease (a group of 7 patients had an isolated complex III defect and a group of 14 patients had a mitochondrial disorder without an isolated complex III defect) and 146 healthy adult control subjects. Gene sequencing was used in the patients, whereas DGGE was performed in the control group. Altogether, 38 variations in the MTCYB gene sequence were identified in the patients and in the control population. The functional relevance of the sequence variations were evaluated using indirect criteria (such as the nature of the mutation, its frequency in controls, and the phylogenetic conservation of the mutated amino acid) and enzymologic and Western blot analysis of complex III. Two original deleterious mutations were found in the group of 7 patients with overt complex III defect. Both mutations (15150G-A; 516020.0008 and 15197T-C; 516020.0009) were heteroplasmic and restricted to muscle tissue and both patients had an isolated intolerance to exercise from their late childhood. Spectrophotometric analysis of the respiratory chain showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. The findings underlined the pathogenic relevance of the 2 heteroplasmic mutations and further confirmed that cytochrome b alterations cause isolated complex III defect in humans. </p><p>Andreu et al. (1998, 1999) noted that mutations in the MTCYB gene are often sporadic and can arise during embryogenesis, affecting a limited number of cells and resulting in tissue-specific phenotypes. Andreu et al. (2000) identified a point mutation in the MTCYB gene (516020.0011) that was associated with histiocytoid cardiomyopathy (500000). </p><p>Fliss et al. (2000) identified a somatic 21-bp deletion in the MTCYB gene in tumor tissue from a patient with bladder cancer (109800). Dasgupta et al. (2008) found that overexpression of the 21-bp deletion identified by Fliss et al. (2000) in murine bladder cancer cells resulted in increased tumor growth and an invasive phenotype in vitro and after injection into mice. Increased tumor growth was associated with shifts toward glycolysis and production of reactive oxygen species (ROS). Rapid cell cycle progression was associated with upregulation of the NFKB (164011) signaling pathway, and inhibition of ROS or NFKB diminished tumor growth in vitro. Transfection of the 21-bp deletion into human uroepithelial cells resulted in similar effects. The findings suggested that mitochondrial mutations may contribute to tumor growth. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, LHON15257A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs41518645,
|
|
|
|
|
|
|
|
ClinVar: RCV000010312, RCV000855257
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This allele changes the highly conserved aspartate at amino acid 171 to an asparagine (D171N). This mutation is located in a region of approximately 20 conserved amino acids that are adjacent to an invariant histidine residue (His-183) that is involved in ligating the low potential b-566 heme (Brown et al., 1992). This allele displays characteristics of both primary and secondary LHON mutations and hence may significantly contribute to the disease process. In most, but not all cases, the MTCYB*LHON15257A allele has been associated with the primary LHON mutation MTND6*LHON14484A and the secondary mutation MTND5*LHON13708A. Individuals harboring this mtDNA haplotype may also harbor the allele MTCYB*LHON15812A, and the MTCYB*LHON15257A allele has been found in association with the MTND2*LHON5244A mutation in 1 case. Overall, individuals carrying the MTCYB*LHON15257A variant make up approximately 9% of LHON patients, but the mutation is also seen in 0.3% of population controls. Families with this variant together with MTND6*LHON14484A have between 27 and 80% of maternal relatives affected, of which between 75 and 100% are males. Approximately 28% of affected individuals experience visual recovery (Brown et al., 1991; Brown et al., 1992; Heher and Johns, 1993; Huoponen et al., 1993; Johns and Neufeld, 1991; Johns et al., 1993). </p><p>Mackey et al. (1996) surveyed 159 families of northern European extraction with at least 1 case of LHON. In 97% of these families, 1 of the 3 previously identified, so-called primary mutations (3460, 11778, and 14484) were found. In no instance was the 15257 mutation found, prompting Mackey et al. (1996) to suggest that it is not a primary mutation causing LHON. They admitted that it might represent a primary causative mutation with penetrance sufficiently high to produce a clear-cut, multigenerational pattern of maternal inheritance. They excluded single cases of LHON from their study. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, LHON15812A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200336777,
|
|
|
|
|
|
|
|
ClinVar: RCV000010313, RCV000855379
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This allele converts the moderately conserved aliphatic amino acid (either alanine, valine, or isoleucine) at 356 to a methionine (V356M). This is a secondary LHON mutation which is regularly found associated with the additional LHON mutations: MTND5*LHON13708A, MTND6*LHON14484A, and MTCYB*LHON15257A. While the mutation does not cause LHON, it may increase the probability of phenotypic expression (Brown et al., 1991; Brown et al., 1992; Johns and Neufeld, 1991). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 14985G-A, ARG80HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207459995,
|
|
|
|
|
|
|
|
ClinVar: RCV000010314, RCV000855200
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Early on, Warburg (1956) suggested that alterations of oxidative phosphorylation in tumor cells play a causative role in cancerous growth. Interest in mitochondria with regard to neoplasia has revived, largely because of their role in apoptosis and other aspects of tumor biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generated in this organelle, coupled with a low level of DNA repair. In a colorectal cancer, Polyak et al. (1998) found 3 somatic mutations in the mitochondrial genome. Two occurred in the MTCYB gene: a 14985G-A change leading to an arg80-to-his substitution; and a 15572T-C transition, leading to a phe276-to-leu substitution (516020.0004). The third mutation occurred in the MTCO1 gene; see 516040.0002. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15572T-C, PHE276LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207459996,
|
|
|
|
|
|
|
|
ClinVar: RCV000010315, RCV002247304
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 516020.0003 and Polyak et al. (1998). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15615G-A, GLY290ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207459997,
|
|
|
|
|
|
|
|
ClinVar: RCV000010316, RCV000855331
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bouzidi et al. (1993) found low activity of respiratory chain complex III in muscle from a 25-year-old man with exercise intolerance in whom Dumoulin et al. (1996) later identified a missense mutation, 15615G-A, in the mitochondrial cytochrome b gene, the only mtDNA encoded subunit of complex III. The findings in this patient were reviewed by Andreu et al. (1999) as part of a series of 9 cases, 5 of their own and 4 reported by others. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 14846G-A, GLY34SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207459998,
|
|
|
|
|
|
|
|
ClinVar: RCV000010317, RCV000855169, RCV002265553, RCV004791206
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of the 5 patients with exercise intolerance due to mutation in the cytochrome b gene of mitochondrial DNA identified by Andreu et al. (1999) was a 52-year-old woman who had had exercise intolerance since childhood with muscle weakness and myopathy on electromyography and hyperlactic acidemia. The patient showed 'ragged-red fibers' (22%) on muscle biopsy. The nucleotide substitution resulted in a gly34-to-ser amino acid substitution. Lactic acidosis in the resting state was found in 4 of the 5 patients studied by Andreu et al. (1999). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ENCEPHALOMYOPATHY, MITOCHONDRIAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15242G-A, GLY166TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207459999,
|
|
|
|
|
|
|
|
ClinVar: RCV000010318, RCV000855252, RCV004691092
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Keightley et al. (2000) presented observations on a 34-year-old woman followed for 17 years. She had a history of progressive exercise intolerance and lactic acidosis starting at approximately 9 years of age. By age 19 years she had clear evidence of encephalopathy, with emotional lability, seizures, abnormal EEG, intermittent visual hallucinations, and depression. The authors identified a stop mutation, 15242G-A, predicting a gly166-to-ter truncation of the protein with loss of 215 amino acids, representing 57% of the C terminus of cytochrome b. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15150G-A, TRP135TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460000,
|
|
|
|
|
|
|
|
ClinVar: RCV000010319, RCV000855232, RCV002247305, RCV004791207
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with isolated intolerance to exercise from late childhood, Legros et al. (2001) identified a nonsense mutation, 15150G-A, predicting a trp135-to-ter truncation of the protein. The family history was negative. The mutation was restricted to muscle tissue where it represented 60% of the mtDNA molecules. The mutation was absent in a control population of 146 healthy adults. Spectrophotometric analysis showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. Western blot analysis of complex III in muscle showed undetectable cytochrome b protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EXERCISE INTOLERANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15197T-C, SER151PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460001,
|
|
|
|
|
|
|
|
ClinVar: RCV000010320, RCV004691093
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with isolated intolerance to exercise from late childhood, Legros et al. (2001) identified a missense mutation, 15197T-C, resulting in a ser151-to-pro amino acid substitution. The serine at position 151 was highly conserved and the mutation constituted an important modification in the physicochemical properties of the amino acid. The family history was negative. The mutation was restricted to muscle tissue where it represented 80% of the mtDNA molecules. The mutation was absent in a control population of 146 healthy adults. Spectrophotometric analysis showed that the complex III activity was extremely decreased in muscle but normal in leukocytes and skin fibroblasts. Western blot analysis of complex III in muscle showed a reduced amount of cytochrome b protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MULTISYSTEM DISORDER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15579A-G, TYR278CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460002,
|
|
|
|
|
|
|
|
ClinVar: RCV000010321, RCV000855325, RCV002247306, RCV003153301
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Whereas most mutations in the MTCYB gene had been reported to cause a homogeneous phenotype of pure exercise intolerance, Wibrand et al. (2001) described a 15579A-G mutation associated with a selective decrease of muscle complex III activity in a patient who, besides severe exercise intolerance, also had multisystem manifestations (deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, epilepsy). The 15579A-G mutation was heteroplasmic in muscle (88%) and leukocytes (15%), and changed a highly conserved tyrosine to cysteine at amino acid position 278. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CARDIOMYOPATHY, INFANTILE HISTIOCYTOID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15498G-A, GLY251ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460003,
|
|
|
|
|
|
|
|
ClinVar: RCV000010322, RCV000855308
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl who died of cardiac arrest at the age of 4 weeks and was found to have typical pathologic features of histiocytoid cardiomyopathy (500000), Andreu et al. (2000) identified a point mutation in the MTCYB gene, a G-to-A transition at nucleotide 15498, resulting in a gly251-to-asp substitution. The mutation, which was heteroplasmic and fulfilled all accepted criteria for pathogenicity, was thought to impair the function of the holoenzyme as deduced from its effects on the crystal structure of ubiquinol cytochrome c oxidoreductase. The infant showed involvement of other organs, including liver (hepatic steatosis) and kidney (acute tubular necrosis). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 14849T-C, SER35PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460004,
|
|
|
|
|
|
|
|
ClinVar: RCV000010323, RCV000855170, RCV002260587
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Schuelke et al. (2002) reported a patient with neurologic symptoms starting in infancy and manifesting as hypotonia, retarded language and motor development, dysdiadochokinesia, gait ataxia, small head circumference, cerebellar hypoplasia, and exercise intolerance. In addition, he had hypertrophic cardiomyopathy, retinitis pigmentosa, and features of septooptic dysplasia; the latter 2 symptoms had not previously been described in association with complex III deficiency. The patient was found to have a 14849T-C mutation in the MTCYB gene, resulting in a substitution of a highly conserved serine for proline at position 35. The mutation was heteroplasmic in muscle (69%) and fibroblasts (12%), although residual complex III activity was the same in both tissues (70%). The authors suggested that the mutation may lead to increased reactive oxygen species, which may play a role in the pathogenic findings. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PARKINSONISM/MELAS OVERLAP SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 4-BP DEL, 14787TTAA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs207460005,
|
|
|
|
|
|
|
|
ClinVar: RCV000010324, RCV003985259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with diminished activity of complex III of the mitochondrial respiratory chain, De Coo et al. (1999) identified a heteroplasmic 4-bp deletion in a highly conserved portion of the cytochrome b gene. The deletion was predicted to lead to a truncated protein. The patient had a severe progressive disorder beginning at age 6 years with difficulty in fine motor coordination and concentration. He later developed behavioral changes, parkinsonism, myoclonus, extensor plantar responses, and cerebral infarcts. More than 95% of the mtDNA in muscle was mutated. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 OBESITY, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCYB, 15497G-A, GLY251SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199951903,
|
|
|
|
|
|
|
|
ClinVar: RCV000022894, RCV000434000, RCV000855307
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Okura et al. (2003) examined the possible relationship between the Mt15497G-A polymorphism and obesity (601665) by studying middle-aged and elderly Japanese individuals (825 women and 906 men). After adjusting for age and smoking, they found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intraabdominal fat, and triglycerides were significantly greater in women with the A allele compared with the G allele. For men, waist-to-hip ratio was significantly greater, and waist circumference, intraabdominal fat, and triglycerides had a trend to be significantly greater, in subjects with the A allele compared with the G allele. These data suggested that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Mitchell (1976)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
|
|
<strong>Sequence and organization of the human mitochondrial genome.</strong>
|
|
Nature 290: 457-465, 1981.
|
|
|
|
|
|
[PubMed: 7219534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290457a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Bruno, C., Dunne, T. C., Tanji, K., Shanske, S., Sue, C. M., Krishna, S., Hadjigeorgiou, G. M., Shtilbans, A., Bonilla, E., DiMauro, S.
|
|
<strong>A nonsense mutation (G15059A) in the cytochrome b gene in a patient with exercise intolerance and myoglobinuria.</strong>
|
|
Ann. Neurol. 45: 127-130, 1999.
|
|
|
|
|
|
[PubMed: 9894887]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1531-8249(199901)45:1<127::aid-art20>3.0.co;2-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Bruno, C., Shanske, S., Shtilbans, A., Hirano, M., Krishna, S., Hayward, L., Systrom, D. S., Brown, R. H., Jr., DiMauro, S.
|
|
<strong>Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy.</strong>
|
|
Neurology 51: 1444-1447, 1998.
|
|
|
|
|
|
[PubMed: 9818877]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.51.5.1444]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Checcarelli, N., Iwata, S., Shanske, S., DiMauro, S.
|
|
<strong>A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy.</strong>
|
|
Pediat. Res. 48: 311-314, 2000.
|
|
|
|
|
|
[PubMed: 10960495]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-200009000-00008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J., DiMauro, S.
|
|
<strong>Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA.</strong>
|
|
New Eng. J. Med. 341: 1037-1044, 1999.
|
|
|
|
|
|
[PubMed: 10502593]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199909303411404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
|
|
<strong>Identification and mapping of human mitochondrial genes.</strong>
|
|
Cytogenet. Cell Genet. 32: 85-98, 1982.
|
|
|
|
|
|
[PubMed: 7140372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000131689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bouzidi, M. F., Schagger, H., Collombet, J. M., Carrier, H., Flocard, F., Quard, S., Mousson, B., Godinot, C.
|
|
<strong>Decreased expression of ubiquinol-cytochrome c reductase subunits in patients exhibiting mitochondrial myopathy with progressive exercise intolerance.</strong>
|
|
Neuromusc. Disord. 3: 599-604, 1993.
|
|
|
|
|
|
[PubMed: 8186719]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0960-8966(93)90123-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Lott, M. T., Voljavec, A. S., Torroni, A., Wallace, D. C.
|
|
<strong>Mitochondrial DNA cytochrome b mutations associated with Leber's hereditary optic neuropathy and evidence for deleterious interactions between mutations. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 49 (suppl.): 973, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C.
|
|
<strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong>
|
|
Genetics 130: 163-173, 1992.
|
|
|
|
|
|
[PubMed: 1732158]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/genetics/130.1.163]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Case, J. T., Wallace, D. C.
|
|
<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
|
|
Somat. Cell Genet. 7: 103-108, 1981.
|
|
|
|
|
|
[PubMed: 6261411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01544751]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G.
|
|
<strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong>
|
|
Nature 314: 592-597, 1985.
|
|
|
|
|
|
[PubMed: 3921850]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/314592a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crivellone, M. D., Wu, M., Tzagoloff, A.
|
|
<strong>Assembly of the mitochondrial membrane system. Analysis of structural mutants of the yeast coenzyme QH2-cytochrome c reductase complex..</strong>
|
|
J. Biol. Chem. 263: 14323-14333, 1988.
|
|
|
|
|
|
[PubMed: 2844766]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Darley-Usmar, V. M., Kennaway, N. G., Buist, N. R. M., Capaldi, R. A.
|
|
<strong>Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 5103-5106, 1983.
|
|
|
|
|
|
[PubMed: 6308671]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.80.16.5103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dasgupta, S., Hoque, M. O., Upadhyay, S., Sidransky, D.
|
|
<strong>Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer.</strong>
|
|
Cancer Res. 68: 700-706, 2008.
|
|
|
|
|
|
[PubMed: 18245469]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1158/0008-5472.CAN-07-5532]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Coo, I. F. M., Renier, W. O., Ruitenbeek, W., Ter Laak, H. J., Bakker, M., Schagger, H., Van Oost, B. A., Smeets, H. J. M.
|
|
<strong>A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.</strong>
|
|
Ann. Neurol. 45: 130-133, 1999.
|
|
|
|
|
|
[PubMed: 9894888]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1531-8249(199901)45:1<130::aid-art21>3.3.co;2-q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dumoulin, R., Sagnol, I., Ferlin, T., Bozon, D., Stepien, G., Mousson, B.
|
|
<strong>A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance.</strong>
|
|
Molec. Cell Probes 10: 389-391, 1996.
|
|
|
|
|
|
[PubMed: 8910895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mcpr.1996.0053]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Esposti, M. D., De Vries, S., Crimi, M., Ghelli, A., Patarnello, T., Meyer, A.
|
|
<strong>Mitochondrial cytochrome b: evolution and structure of the protein.</strong>
|
|
Biochim. Biophys. Acta 1143: 243-271, 1993.
|
|
|
|
|
|
[PubMed: 8329437]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0005-2728(93)90197-n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fliss, M. S., Usadel, H., Caballero, O. L., Wu, L., Buta, M. R., Eleff, S. M., Jen, J., Sidransky, D.
|
|
<strong>Facile detection of mitochondrial DNA mutations in tumors and bodily fluids.</strong>
|
|
Science 287: 2017-2019, 2000.
|
|
|
|
|
|
[PubMed: 10720328]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.287.5460.2017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: 6256757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.77.11.6715]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonzalez-Halphen, D., Lindorfer, M. A., Capaldi, R. A.
|
|
<strong>Subunit arrangement in beef heart complex III.</strong>
|
|
Biochemistry 27: 7021-7031, 1988.
|
|
|
|
|
|
[PubMed: 2848575]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00418a053]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hatefi, Y.
|
|
<strong>The mitochondrial electron transport and oxidative phosphorylation system.</strong>
|
|
Annu. Rev. Biochem. 54: 1015-1069, 1985.
|
|
|
|
|
|
[PubMed: 2862839]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.54.070185.005055]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hayes, D. J., Lecky, B. R. F., Landon, D. N., Morgan-Hughes, J. A., Clark, J. B.
|
|
<strong>A new mitochondrial myopathy: biochemical studies revealing a deficiency in the cytochrome b-c1 complex (complex III) of the respiratory chain.</strong>
|
|
Brain 107: 1165-1177, 1984.
|
|
|
|
|
|
[PubMed: 6095966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/107.4.1165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heher, K. L., Johns, D. R.
|
|
<strong>A maculopathy associated with the 15257 mitochondrial DNA mutation.</strong>
|
|
Arch. Ophthal. 111: 1495-1499, 1993.
|
|
|
|
|
|
[PubMed: 8240104]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.1993.01090110061024]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huoponen, K., Lamminen, T., Juvonen, V., Aula, P., Nikoskelainen, E., Savontaus, J. L.
|
|
<strong>The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy.</strong>
|
|
Hum. Genet. 92: 379-384, 1993.
|
|
|
|
|
|
[PubMed: 7901141]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01247339]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.
|
|
|
|
|
|
[PubMed: 1764087]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)92088-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Smith, K. H., Savino, P. J., Miller, N. R.
|
|
<strong>Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation.</strong>
|
|
Ophthalmology 100: 981-986, 1993.
|
|
|
|
|
|
[PubMed: 8321540]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0161-6420(93)31527-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. M., Kennaway, N. G.
|
|
<strong>Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.</strong>
|
|
Am. J. Hum. Genet. 67: 1400-1410, 2000.
|
|
|
|
|
|
[PubMed: 11047755]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/316900]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kennaway, N. G., Buist, N. R., Darley-Usmar, V. M., Papadimitriou, A., Dimauro, S., Kelley, R. I., Capaldi, R. A., Blank, N. K., D'Agostino, A.
|
|
<strong>Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain.</strong>
|
|
Pediat. Res. 18: 991-999, 1984.
|
|
|
|
|
|
[PubMed: 6093035]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-198410000-00017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Legros, F., Chatzoglou, E., Frachon, P., de Baulny, H. O., Laforet, P., Jardel, C., Godinot, C., Lombes, A.
|
|
<strong>Functional characterization of novel mutations in the human cytochrome b gene.</strong>
|
|
Europ. J. Hum. Genet. 9: 510-518, 2001.
|
|
|
|
|
|
[PubMed: 11464242]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200678]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Linke, P., Weiss, H.
|
|
<strong>Reconstitution of ubiquinol-cytochrome c reductase from Neurospora mitochondria with regard to subunits I and II.</strong>
|
|
Methods Enzymol. 126: 201-210, 1986.
|
|
|
|
|
|
[PubMed: 2856127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0076-6879(86)26022-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mackey, D. A., Oostra, R.-J., Rosenberg, T., Nikoskelainen, E., Bronte-Stewart, J., Poulton, J., Harding, A. E., Govan, G., Bolhuis, P. A., Norby, S., Bleeker-Wagemakers, E. M., Savontaus, M.-L., Chan, C., Howell, N.
|
|
<strong>Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. (Letter)</strong>
|
|
Am. J. Hum. Genet. 59: 481-485, 1996.
|
|
|
|
|
|
[PubMed: 8755941]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mitchell, P.
|
|
<strong>Possible molecular mechanisms of the proton motive function of cytochrome systems.</strong>
|
|
J. Theor. Biol. 62: 327-347, 1976.
|
|
|
|
|
|
[PubMed: 186667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-5193(76)90124-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mitchell, P.
|
|
<strong>Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity.</strong>
|
|
Biochem. Soc. Trans. 4: 399-430, 1976.
|
|
|
|
|
|
[PubMed: 137147]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bst0040399]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: 7219535]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290465a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan-Hughes, J. A., Hayes, D. J., Clark, J. B., Landon, D. N., Swash, M., Stark, R. J., Rudge, P.
|
|
<strong>Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain.</strong>
|
|
Brain 105: 553-582, 1982.
|
|
|
|
|
|
[PubMed: 7104666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/105.3.553]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: 7219536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290470a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okura, T., Koda, M., Ando, F., Niino, N., Tanaka, M., Shimokata, H.
|
|
<strong>Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population.</strong>
|
|
Hum. Genet. 113: 432-436, 2003.
|
|
|
|
|
|
[PubMed: 12905068]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-003-0983-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: 6438810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01535230]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: 6955589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.2.1.30-41.1982]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oudshoorn, P., Van Steeg, H., Swinkels, B. W., Schoppink, P., Grivell, L. A.
|
|
<strong>Subunit II of yeast QH2:cytochrome-c oxidoreductase. Nucleotide sequence of the gene and features of the protein..</strong>
|
|
Europ. J. Biochem. 163: 97-103, 1987.
|
|
|
|
|
|
[PubMed: 3028797]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1432-1033.1987.tb10741.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong>
|
|
Nature Genet. 20: 291-293, 1998.
|
|
|
|
|
|
[PubMed: 9806551]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/3108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rana, M., de Coo, I., Diaz, F., Smeets, H., Moraes, C. T.
|
|
<strong>An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production.</strong>
|
|
Ann. Neurol. 48: 774-781, 2000.
|
|
|
|
|
|
[PubMed: 11079541]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rieske, J. S.
|
|
<strong>Composition, structure, and function of complex III of the respiratory chain.</strong>
|
|
Biochim. Biophys. Acta 456: 195-247, 1976.
|
|
|
|
|
|
[PubMed: 788795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0304-4173(76)90012-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saraste, M.
|
|
<strong>Location of haem-binding sites in the mitochondrial cytochrome b.</strong>
|
|
FEBS Lett. 166: 367-372, 1984.
|
|
|
|
|
|
[PubMed: 6363134]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(84)80114-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schagger, H., Link, T. A., Engel, W. D., von Jagow, G.
|
|
<strong>Isolation of the eleven protein subunits of the bc1 complex from beef heart.</strong>
|
|
Methods Enzymol. 126: 224-237, 1986.
|
|
|
|
|
|
[PubMed: 2856130]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0076-6879(86)26024-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schuelke, M., Krude, H., Finckh, B., Mayatepek, E., Janssen, A., Schmelz, M., Trefz, F., Trijbels, F., Smeitink, J.
|
|
<strong>Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.</strong>
|
|
Ann. Neurol. 51: 388-392, 2002.
|
|
|
|
|
|
[PubMed: 11891837]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10151]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spiro, A. J., Moore, C. L., Prineas, J. W., Strasberg, P. M., Rapin, I.
|
|
<strong>A cytochrome-related inherited disorder of the nervous system and muscle.</strong>
|
|
Arch. Neurol. 23: 103-112, 1970.
|
|
|
|
|
|
[PubMed: 5430330]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1970.00480260009002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tzagoloff, A., Wu, M. A., Crivellone, M.
|
|
<strong>Assembly of the mitochondrial membrane system. Characterization of COR1, the structural gene for the 44-kilodalton core protein of yeast coenzyme QH2-cytochrome c reductase.</strong>
|
|
J. Biol. Chem. 261: 17163-17169, 1986.
|
|
|
|
|
|
[PubMed: 3023384]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the committee on human mitochondrial DNA. In: Cuticchia, A. J.; Pearson, P. L. (eds.): Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461, 1986.
|
|
|
|
|
|
[PubMed: 3518425]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warburg, O.
|
|
<strong>On the origin of cancer cells.</strong>
|
|
Science 123: 309-314, 1956.
|
|
|
|
|
|
[PubMed: 13298683]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.123.3191.309]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weiss, H., Linke, P., Haiker, H., Leonard, K.
|
|
<strong>Structure and function of the mitochondrial ubiquinol: cytochrome c reductase and NADH: ubiquinone reductase.</strong>
|
|
Biochem. Soc. Trans. 15: 100-102, 1987.
|
|
|
|
|
|
[PubMed: 3030833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bst0150100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wibrand, F., Ravn, K., Schwartz, M., Rosenberg, T., Horn, N., Vissing, J.
|
|
<strong>Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene.</strong>
|
|
Ann. Neurol. 50: 540-543, 2001.
|
|
|
|
|
|
[PubMed: 11601507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.1224]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wikstrom, M., Krab, K., Saraste, M.
|
|
<strong>Proton-translocating cytochrome complexes.</strong>
|
|
Annu. Rev. Biochem. 50: 623-655, 1981.
|
|
|
|
|
|
[PubMed: 6267990]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.50.070181.003203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wikstrom, M., Krab, K.
|
|
<strong>The semiquinone cycle. A hypothesis of electron transfer and proton translocation in cytochrome bc-type complexes.</strong>
|
|
J. Bioenerg. Biomembr. 18: 181-193, 1986.
|
|
|
|
|
|
[PubMed: 3015895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00743463]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 10/23/2008<br>Victor A. McKusick - updated : 10/1/2003<br>Cassandra L. Kniffin - updated : 9/18/2003<br>Cassandra L. Kniffin - updated : 8/13/2002<br>Cassandra L. Kniffin - updated : 7/8/2002<br>Victor A. McKusick - updated : 4/23/2002<br>Victor A. McKusick - updated : 12/13/2001<br>Michael B. Petersen - updated : 11/28/2001<br>Victor A. McKusick - updated : 12/13/2000<br>Victor A. McKusick - updated : 10/6/1999<br>Victor A. McKusick - updated : 6/17/1998<br>Douglas C. Wallace - updated : 4/6/1994
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 3/2/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 05/05/2022<br>carol : 05/04/2022<br>carol : 03/18/2022<br>carol : 07/28/2015<br>terry : 5/24/2011<br>terry : 3/23/2011<br>terry : 3/23/2011<br>terry : 3/23/2011<br>terry : 3/22/2011<br>ckniffin : 11/24/2010<br>carol : 1/19/2010<br>wwang : 10/24/2008<br>ckniffin : 10/23/2008<br>ckniffin : 10/23/2008<br>terry : 4/6/2005<br>alopez : 10/6/2003<br>terry : 10/1/2003<br>carol : 10/1/2003<br>ckniffin : 9/18/2003<br>ckniffin : 1/3/2003<br>carol : 8/22/2002<br>ckniffin : 8/13/2002<br>carol : 8/9/2002<br>ckniffin : 8/9/2002<br>carol : 8/9/2002<br>ckniffin : 7/8/2002<br>terry : 6/27/2002<br>mgross : 4/26/2002<br>terry : 4/23/2002<br>alopez : 12/13/2001<br>cwells : 12/5/2001<br>cwells : 11/28/2001<br>terry : 1/19/2001<br>mcapotos : 1/9/2001<br>mcapotos : 12/27/2000<br>terry : 12/13/2000<br>terry : 11/24/1999<br>carol : 10/6/1999<br>jlewis : 6/23/1999<br>jlewis : 6/23/1999<br>jlewis : 6/22/1999<br>jlewis : 6/21/1999<br>carol : 2/24/1999<br>terry : 6/18/1998<br>terry : 6/17/1998<br>dholmes : 5/11/1998<br>dholmes : 5/11/1998<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>mimadm : 5/17/1994<br>pfoster : 5/12/1994<br>carol : 2/28/1994<br>carol : 5/26/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|